(a) Field of the Invention
The present invention is directed to novel topical pharmaceutical gel compositions of diclofenac sodium. The topical compositions comprise at least about 10% w/w of diclofenac sodium and are suitable for once-a-day application. The invention is further directed to the use of said compositions for treating painful conditions, inflammations and/or rheumatic diseases or providing relief of the pain of osteoarthritis of joints amenable to topical treatment, such as the knees, ankles, feet, elbows, wrists, hands, spine, hip, and shoulder. Additionally, the present invention provides a method of manufacture of said composition.
(b) Description of the Related Art
Delivery of active agents across the skin or mucosal membrane is convenient, pain-free, non-invasive and circumvents problems associated with the “first pass effect”. Such transdermal or topical drug delivery is typically restricted to low molecular weight drugs and drugs with specific lipophilic/hydrophilic balance able to penetrate the stratum corneum.
Transdermal drug delivery systems enable chemical modification of the barrier properties of the skin to effectively and efficiently permit permeation thereof. Known drawbacks of transdermal delivery systems are, for example, the length of time needed for permeation, a frequent dosing regimen, and the volume size of a transdermal composition needed to transdermally deliver a sufficient therapeutic amount of the active agent.
Diclofenac (2-(2,6-dichloranilino) phenylacetic acid) is a non-steroidal anti-inflammatory drug (NSAID) used to reduce inflammation and, as an analgesic, to reduce pain. It is available in the sodium, potassium, epolamine and diethylamine salt forms in numerous dosage forms (oral tablet, oral syrup, topical gel, cataplasm, ophthalmic drop, suppository, etc.).
An example of a well-known transdermal diclofenac formulation is Voltaren® Gel 1 which comprises 1% diclofenac sodium. Voltaren® is indicated in the USA for the relief of the pain due to osteoarthritis of joints amenable to topical treatment, including the knees, ankles, feet, elbows, wrists, and hands. Up to 4 gm of Voltaren® gel can be applied to lower extremities (including the knees, the ankles, and the feet) 4 times daily so that up to not more than 16 gm daily of Voltaren® Gel 1% is applied to any single joint of the lower extremities. Up to 2 gm of Voltaren® Gel 1% can also be applied to the upper extremities (which include the elbows, the wrists and the hands) 4 times daily so that up to not more than 8 gm daily of Voltaren® Gel 1% is applied to any single joint of the upper extremities. Overall, the total dose of Voltaren® Gel 1% should not exceed 32 gm per day over all affected joints. Neither the total amount (up to 32 gm per day) nor the frequency of application (4 times a day) are satisfactory from a patient perspective.
U.S. Pat. No. 7,335,379 discloses formulations for transdermal or transmucosal administration of active agents, such as diclofenac, containing an alkanol, a polyalcohol, a monoalkyl ether of diethylene glycol and a fatty alcohol with a fatty alcohol content of up to 2%.
U.S. Pat. No. 4,543,251 discloses an external gel formulation containing 0.3 to 3% w/w of diclofenac sodium having good stability.
PCT Application Publication No. 2014009241 discloses diclofenac gel formulations containing 1% and 3% diclofenac sodium, C2 to C4 alkanol, monoalkyl ether of diethylene glycol and fatty alcohol.
U.S. Pat. No. 7,132,452 discloses topical formulations containing NSAID, particularly diclofenac for alleviating pain/inflammation associated with infection caused by herpes virus. The amount of diclofenac in the formulation can be 1-10% w/w of the entire formulation. The patent further discloses that the formulation provides a complete relief on application for seven days.
EP 1,890,687 B1 discloses topical gel formulations of diclofenac sodium for relief of pain and inflammation. According to the patent the formulation may contain up to 10% w/w of diclofenac.
None of the prior art reference disclose or suggest topical gel formulation containing high amount of diclofenac sodium, let alone its therapeutic benefits on once-a-day application.
There remains a need for topical compositions of diclofenac containing relatively higher amount of diclofenac sodium which are effective for treating painful conditions, inflammations, and specifically providing fast and effective treatment for alleviating symptoms relating to the pain of osteoarthritis of joints. On comparing to the topical treatment of Voltaren® Gel 1% or other commercially available 3% diclofenac gel formulations, the topical composition of the present invention on once-a-day application provided relief that is comparable to that achieved with 4 times daily application of currently known 1% w/w or 3% w/w diclofenac gel formulations.